O o-dimethyl phosphorothioate esters of methyl pyrazinols as insecticides

ABSTRACT

INSECTICIDAL COMPOUNDS ARE PROVIDED HAVING THE FORMULA:   2-((CH3-O-)2-P(=S)-O-),(CH3-)2-PYRAZINE   THIS IS A DIVISIONAL APPLICATION OF APPLICATION. SER. NO. 762,379, FILED SEPT. 16, AND NOW ISSUED AS U.S. PAT. NO. 3,505,328.

United States Patent Oflice 3,644,621 Patented Feb. 22, 1972 Int. Cl. A01n 9/36 US. Cl. 424200 Claims ABSTRACT OF THE DISCLOSURE Insecticidal compounds are provided having the for- This is a divisional application of application Ser. No. 762,379, filed Sept. 16, 1968, and now issued as US. Pat. No. 3,505,328.

SUMMARY OF THE INVENTION This invention relates to 0,0-dimethyl phosphorothioate esters of methyl pyrazinols which have the formula:

This invention also pertains to the use of the compounds as insecticides and acaricides.

BACKGROUND OF THE INVENTION The compounds of this invention are embraced within the generic disclosure of compounds given in US. Pats. 2,918,468; 2,938,831; 3,091,614; and 3,340,262. They are, however, not specifically disclosed in any of these patents.

Applicants have now discovered that the compounds of this invention possess unusual properties not generally shared by the large number of compounds embraced within the generic formula of the above patents. More particularly, applicant has discovered that, when compared to the compounds disclosed in the above patents, the inventive compounds (I) possess substantially lower mammalian toxicity, (2) are significantly more potent toward certain difficult to control insects which ravage cotton and other economic crops and (3) exhibit substantially greater activity, including residual activity, against the alfalfa weevil.

The unusual properties discussed above will be exemplified hereinbelow by comparative data with structurally similar compounds and other promising compounds of the above patents, said compounds hereinafter called prior art compounds.

DESCRIPTION OF THE PREFERRED EMBODIMENTS The following are illustrative of the compounds of this invention:

0,0-dimethyl-O-(3,5-dimethyl-2-pyrazinyl) phosphorothioate 0,0-dimethyl-O-(5,6-dimethyl-2-pyrazinyl) phosphorothioate 0,0-dimethyl-O-(3,6-dimethyl-2-pyrazinyl) phosphorothioate The compounds are readily prepared by techniques shown in US. Pats. 2,918,468; 2,938,831; 3,091,614; and 3,340,262, said patents herein incorporated by reference. The compounds may also be prepared by reacting dimethyl phosphorochloridothioate with the appropriate methyl substituted hydroxypyrazine in the presence of potassium tertiary butoxide (about one mole per mole of hydroxypyrazine) and dimethylsulfoxide solvent at temperatures of 20 to 60 C.

The compounds of this invention are useful for controlling a variety of insects and acarides such as those shown in the examples provided hereinbelow. They may be applied to the foliage of plants as dusts or liquid sprays to protect them from insects which feed thereon; they may also be incorporated in or applied to the soil in order to protect germinating and growing plants from soil-borne pests which attack the root systems and stems of said plants; or they may be applied to the breeding sites of pests to control both the larvae and adult stages of breeding pest populations. In the latter situations the compounds may be applied in conventional formulations such as dusts, dust concentrates, granular materials, wettable powders, emulsifiable concentrates and the like. They may be employed as an emulsion in water or other non-solvents to which suitable surfactants, wetting agents or emulsifying agents have been added. They may be applied on solid carriers, such as tales and clays, as for example kaolin clay or fullers earth, or on such carriers as chalk, wood flour, silica, charcoal, activated carbon or other inert powders. As a wettable powder, the compound of this invention may be applied to easily wettable carrier materials, such as attaclay, with or Without the aid of surfactants, or on less readily wettable carriers in combination with suitable surfactants.

Advantageously, the compounds of the invention may also be applied by the most modern techniques of low volume or ultra-low volume application wherein the compound is applied essentially as a technical material or in combination with a minor amount of hydrocarbon solvent such as Panasol AN-S, Socal 44-L or Esso HAN (all commercially available).

The compounds of this invention may also be applied in combination with other essentially technical materials, such as malathion, which in addition to having insecticidal properties also serve as a formulation vehicle.

The following examples are provided to further illustrate the unusual properties exhibited by the compounds of this invention.

COMPARATIVE EXAMPLE l.MAMMALIAN TOX- ICITY AND GENERAL INSECTICIDAL AC- TIVITY (A) Bean aphidAphis fabae Scopoli Compounds are tested as 0.1% solutions or suspensions in 65% acetone-34% water. Two-inch fiber pots, each containing a nasturtium plant two inches high and infested with about 150 aphids two days earlier, are placed on a turntable (4 r.p.m.) and sprayed for two revolutions with a #154 DeVilbiss Atomizer at 20 p.s.i. air pressure. The spray tip is held about six inches from the plants and the spray is directed so as to give complete coverage of the. aphids and the plants. The sprayed plants are laid on their sides on white enamel trays which have had the edges coated with #50 SAE oil as a barrier. Mortality estimates are made after holding for two days at 70 F., and 50% RH.

(B) Southern armywormProdenia eridania (Cramer) The solutions from the aphid test are also used for this one. Sieva lima bean primary leaves are dipped for three seconds in the test solution and set in a hood on a screen to dry. When dry, each leaf is placed in a 4-inch petri dish which has a moist filter paper in the bottom and ten third-instar armyworm larvae about long. The dishes are covered and held at 80 F., and 60% RH. After 2 days, mortality counts and estimates of the amount of feeding are made.

(C) Two-spotted spider mite-Tetrany'chus urticas (Koch) Sieva lima bean plants with primary leaves three to four inches long are infested with about 100 adult mites per leaf four hours before use in this test. The mite and egg infested plants are dipped for three seconds in the same solutions used in the above tests, and the plants set in the hood to dry. They are held for two days at 80 F., 60% r.h., and the adult mite mortality estimated on one leaf under a stereoscopic microscope. The other leaf is left on the plant an additional five days and then examined at X power to estimate the kill of eggs and of newlyhatched nymphs, giving a measure of ovicidal and residual action, respectively.

(D) Confused flour beetle-Tribolium confusum Jacquelin duVal Compounds are formulated as 1% dusts by mixing 0.1 gram of the compound with 9.9 grams of Pyrax ABB talc, wetting with 5 H11. of acetone and grinding with. a mortar and pestle until dry. 125 mg. of this 1% dust is then blown into the top of a dust settling tower with a short blast of air at p.s.i. The dust is allowed to settle on four-inch petri dishes for two minutes, giving a deposit of approximately 87 mg./sq. foot (.094 mg./sq. cm.) of the 1% dust. The dishes are removed and adult confused flour beetles are added immediately. The dishes are held for three days at 80 F. and 60% RH, following which mortality counts are made.

(E) Large milkweed bug-Onc0peltus fasciatus Dallas The 1% dusts described above are used in this test. 25 mg. of the 1% dust is sprinkled evenly over the glass bottom of a seven-inch diameter cage, using a screenbottom plastic cup about in diameter as an app1icator, giving a deposit of approximately 94 mg./sq. ft. (.108 mg./sq. cm.) of the 1% dust. Water is supplied in a two-ounce bottle with a cotton wick, twenty adult bugs are added and a screen cover placed on the top. Mortality counts are made after holding for three days at 80 F. and 60% RH.

(F) German cookroach--Blattella germanica (Linnaeus) The procedure is the same as for the large milkweed bug test, except that in this test only adult males are used.

(G) Systemic tests The compound to be tested is formulated as an emulsion containing 0.1 gram of test material, 0.2 gram of Alrodyne 315 emulsifier, 10 ml. of acetone and 90 ml. of water. This is diluted ten-fold with water to give a 100 p.p.m. emulsion for the initial test. A sieva lima bean plant with only the primary leaves unfolded is I cut 01f just above soil level and inserted into a two ounce bottle of 100 ppm. emulsion and held in place by a bit of cotton wrapped around the stem. The bottle is then placed in a ventilated box with the leaves extending outside the box, such that any possible fumes from the compound will be drawn out the end of the box rather than rising to affect the test leaves. About 50 adult two-spotted spider mites are placed on each leaf. After holding three days at F. and 60% R.H., mortality estimates are made and one leaf from each plant is placed on a moist filter paper in the bottom of a petri dish. Ten third-instar southern armyworm larvae are added to each dish and mortality counts made after holding another three days at 80 F. and 60% RH.

(H) Common malaria mosquito-An0pheles quadrimaculatus Say (1) Larvicide test.-Groups of 25 larvae of the common malaria mosquito are transferred with a medicine dropper to a 50 ml. beaker containing 25 ml. of water. The test compound is formulated as an emulsion containing 0.1 gram of test material, 0.2 gram of Alrodyne 315 emulsifier, 10 ml. of acetone and ml. of water. This 1000 p.p.m. emulsion is diluted ten-fold with 65% acetone-35% water to give p.p.m. One milliliter of the 100 ppm. emulsion is pipetted into 225 ml. of water in a 400 ml. beaker and stirred vigorously. The larvae in 25 ml. of water are added, giving a concentration of 0.4 p.p.m. Mortality counts are made after 24 hours at 80 F.

(2) Adulticide test.-Test compounds are prepared as 10 p.p.m. solutions in acetone. Glass microscope slides are dipped in the test solutions and allowed to dry in a horizontal position. When dry, they are individually placed in four-ounce wide mouth bottles and ten 4- to 5-day old mosquitoes of mixed sexes are added to each bottle. A piece of cotton gauge serves as a lid, and a wad of cotton soaked in 10% sugar solution serves as food. Mortality counts are made after 24 hours of continuous exposure to the residue on the glass slide; tem perature is 80 F. and RH. is 60%.

(I) HouseflyMusca domestica Linnaeus Groups of 25 adult female houseflies are lightly anesthetized with CO placed in wide-mouth pint mason jars, and covered with a screen cap. The test compound is formulated as an emulsion containing 0.1 gram of test material, 0.2 gram of Alrodyne 315 emulsifier, 10 ml. of acetone and 90 ml. of water. Two milliliters of this emulsion are diluted to 40 ml. with 10% sugar solution in a IO-gram glass vial, giving a concentration of 50 p.p.m. The mouth of the vial is covered with a single layer of cheesecloth, inverted and placed on the screen cap, so that the flies can feed on the solution through the screen. Mortality counts are made after two days at 80 F.

(J) Southern corn 1'00tWOrmDiabr0tica zmdecimpzmctata howardz' Barber The compound is formulated as a dust and incorporated into the soil at the equivalent of 10 pounds per 6-inch acre. The soil is sub-sampled into one-ounce wide mouth bottles, and ten 6 to 8-day old rootworm larvae added to each bottle, which is then capped. Mortality counts are made after six days at 80 F., 60% RH.

(K) False wirewormEIc0des suturalis Say The test is the same as with the rootworm except that 10 day old wireworm larvae are used.

LD values are measured in accordance with standardized and well known procedures which do not bear repeating herein.

Results are shown in Table I.

7 ACTIVITY AGAINST INSECTS OF THE COTTON COMPLEX The compounds of this invention have been found to possess an unusually high activity against certain pests which ravage cotton and other economic crops. Such pests will be referred to hereafter as the cotton complex of insects, said cotton complex comprising insects selected from the group consisting of lygus, tobacco budworm, bollworm (also commonly referred to as corn earworm TABLE II.ACTIVITY AGAINST TOBACCO BUDWORM ao Number Compound g/larva) This invention 1 H N 35 ousonr-o-f CH3 OH a II N onno iro-f oHt \N CH;

orI30 ,r-o-( CH;

\N Prior art; compounds o2H.o 2P o- \OH3 (C2II O)zP-O i and tomato fruitworm), and boll weevil. The boll weevil is essentially a cotton pest; however, lygus, tobacco budworm, and bollworm not only ravage cotton, but also such important economic crops as beans, soybeans, green beans, snapbeans, corn, alfalfa, tomatoes, tobacco, safflower, and clover. Thus, despite classification within the cotton complex, it must be understood that lygus, tobacco budworm, and bollworm are a threat to a variety of crops in addition to cotton, and that the unusually high potency shown by the compounds of this invention is directed toward the insects of the cotton complex per se and is substantially independent of the vegetative environment in which the insect happens to be found.

The cotton complex of pests is known to be extremely difficult to destroy by treatment with chemical agents. This ditficulty is believed due to the ability of these particular insects to develop a resistance to the various chemicals used against them.

The unusual activity of the compounds of this invention against the difficult to control cotton complex of insects is exemplified by the data presented in comparative Examples 2 and 3 hereinbelow.

COMPARATIVE EXAMPLE 2.ACTIVITY AGAINST TOBACCO BUDWORM Helz'othis virescens (tobacco budworm) is placed in a one-ounce plastic medicine cup containing about grams of artificial diet used for rearing tobacco budworms. Each budworm is treated topically on the dorsal surface with 0.96 ,ul. of acetone containing 40, or 10 g. of compound. lf the mortality at the lowest rate is 50% or more, each succeeding concentration is reduced /2 until the activity is nil. The data are plotted on dosage-response logarithmic paper from which an LD is determined.

As indicated by the data of Table II above, the inventive compounds appear particularly active against the tobacco budworm. In analyzing the data of Table II, it must be pointed out that since the objective is to destroy the tobacco budworm, low LD values are desirable since the lower the LD value observed, the greater the toxicity of the compound against the tobacco budworm. This, of course, is in contrast to the usual mammalian toxicity data wherein higher LD values are desirable since they are an indication of lower toxicity toward human beings.

Referring to Table II, it can be seen that inventive compound 1, when applied topically to the budworm, is about 18.5 times more effective than compound 2, its ethoxy homolog. Similar effects are noted when compound 1 is compared with related prior art compounds 3 (2 times more effective), and 4 (15.8 times more effective).

The inventive compounds are substantially more effective against tobacco budworm than compound 5 which is Zinophos Nematocide.

COMPARATIVE EXAMPLE 3.--ACTIVITY AGAINST LYGUS AND BOLL WEEVIL (1) Tarnished plant bugLygus lineolaris (Palisot de Beauvois) Test compounds are prepared as 10 ppm. solutions in 10% acetone, 0.2% Alrodyne 315, and 89.8% water. The primary leaves of Sieva lima bean plants are dipped for 3-5 seconds in the test solutions and placed in an exhaust hood to dry. When dry, each leaf is placed in a 4-inch petri dish with a moist filter paper on the bottom. Ten adult lygus bugs are aspirated from the stock culture and placed in the petri dish. The dishes are covered and held at F. and 60% RH. After 2 days, mortality counts are made.

(2) Boll weevilAnthonmus grandis Boheman Test compounds are prepared as p.p.m. solutions in 10% acetone, 0.2% Alrodyne 315, and 89.8% water. The first or second true leaf of young cotton plants is dipped for 3-5 seconds in the test solution and placed in an exhaust hood to dry. When dry, each leaf is placed in a 4-inch petri dish with a moist filter paper on the bottom. Ten adult boll weevils are removed from the stock culture and placed in the petri dish. The dishes are covered and held at 80 F. and RH. After 2 days, mortality counts are made.

Results are shown in Table III below:

ACTIVITY AGAINST THE ALFALFA WEEVIL In recent years the alfalfa weevil has become a major threat to the production of alfalfa. Previously held under control by chlorinated hydrocarbon insecticides, the alfal- TABLE III.-ACIIVITY AGAINST LYGUS AND BOLL WEEVIL Mortality at 10 Number Compound This invention 1 s II N carom-0T wforn s H N mounonr-o-F 7 s I] N rumour-0f I CH3 s ll N outflow-0T 10113 Prior art compounds N alumni-01 H-om The efiicacy of the inventive compounds against lygus and boll weevil is clearly exemplified by the data shown in Table III above.

Inventive compound 1 exhibits 100% kill of lygus at a dosage of 10 ppm. while related prior art compounds 2 (the ethoxy homolog), 3 (the n-propyl homolog), and 4 (the isopropyl homolog) are devoid of any activity whatsoever against lygus. In this connection, it should be noted that when the ethoxy groups of compound 2 are merely replaced by methoxy groups to thereby produce the compounds of this invention, the percent kill of lygus jumps remarkably from 0 to 100%.

Although less closely related prior art compounds 5, 6, and 7 are active against lygus, they are totally inactive against the boll weevil. Inventive compound 1 is, in fact, the only compound in Table III which shows any activity whatsoever against boll weevil. The data of Table III thus p.p.m., percent Boll Lygus weevil 60 fa Weevil has not only become resistant to these measures but adverse residues which show up in the milk of dairy animals have caused the removal of registrations of these materials for this use. Therefore, effective safe materials are needed to control this pest which do not leave harmful residues.

COMPARATIVE EXAMPLE 4.ACTIVITY AGAINST THE ALFALFA WEEVIL A field study was conducted to determine the elfectiveness of the compounds of this invention in comparison to Zinophos Nematocide and malathion for the control of the alfalfa weevil larvae. Each material formulated as an emulsifiable concentrate was applied to 10 x 50 foot plots of heavily infested alfalfa. The inventive compounds and Zinophos were applied at a rate of 0.5 lb. actual insecticide per acre and compared to a standard treatment of 1 l malathion at 1.25 lbs. actual insecticide per acre. The materials were applied with a tractor mounted sprayer fitted with a foot boom calibrated to deliver gallons of water diluted spray per acre.

At intervals of 8, 14 and 21 days after spraying, alfalfa weevil larvae were collected from each plot by making 10 random sweeps across the tops of the plants with a sweep net. The number of larvae per 10 sweeps per plot were determined and compared to untreated plots. The percent control in the treated plots was determined using Abbotts formula as follows:

X 100=percent control Where X=number of live larvae in untreated plots. Y==nurnber of live larvae in treated plots.

Results are shown below in Table IV.

S n N s z t I n CH3 2. A method for protecting vegetation from destruction by insects and acarides which comprises applying to said TABLE IV.-FIELD EVALUATION AGAINST ALFALFA WEEVIL LARVAE Rate of Percent control of alfalfa weevil applllarvae at various intervals tion after treatment (1bs./ Number Compound acre) 8 days 14 days 21 days This invention 1 8]: N 0. 5 99. 0 93. 8 63. 1

oraonP-o 4 CH3 LN CH3 u ,N C2H.0)2P0- Pd t d Zlnophos or 9.1 com oun p 3 H (H) 1. 25 77. 0 73. 3 31. 3

(CH3O)zPS-CHCO 0 H,

CH2(I'IJO (3 H,

(malathlon) 1 Corrected by Abbott's formula.

The unusual activity of the compounds of this invention against the alfalfa weevil is clearly exemplified by the data presented in Table IV above. It is apparent from these data that compound 1, at 0.5 lb. actual insecticide per acre, gives superior initial and residual control of alfalfa weevil larvae than an equal rate of Zinophos Nematocide or 1.25 lbs. of actual malathion per acre.

EXAMPLE 5 .-PREPARATION OF 0,0-DIMETHYL- O-(5,6 DIMETHYL-Z-PY' RAZLNY'L) PHOSPHORO- THIOATE s on, o r-ofiji CH: 1 on,

To 6 parts of sodium 5,6-dimethyl pyrazinolate in 158 parts of tert-butyl alcohol was added 6.6 parts of 0,0- dimethyl phosphorochloridothioate. After stirring at ambient temperature for three hours, the tert-butyl alcohol was distilled under reduced pressure. The residual dark oil was dissolved in CCl filtered, and purified by adsorp- References Cited UNITED STATES PATENTS 2,918,468 12/1959 Dixon et al. 260--250 3,091,614 9/1963 Miller et al. 260-250 3,340,262 9/1967 Gagliardi 260250 ALBERT T. MEYERS, Primary Examiner L. SCHENKMAN, Assistant Examiner 

